The overall objective of the proposed research is to obtain important information concerning the structural characteristics, distribution, and mechanisms of actions of the gastrointestinal hormones of man in health and disease. Immunochemical techniques will be utilized to examine and characterize the synthesis and release of gastrin by application of in vitro methods. The effects of calcium, hormones, and activator substances on synthesis and release of gastrin by antral and duodenal mucosal tissues from normal man and patients with diseases of the upper gastrointestinal tract, including duodenal ulcer disease, will be examined. Immunochemical methods will be applied to the clarification of the multiple species of gastrin in the circulation, species which may vary in their molecular size, charge characteristics, biological activity, and structural relationship with well characterized gastrin heptadecapeptides. The distribution of cells containing gastrin, secretin, and cholecystokinin-pancreozymin in the mucosa of the upper gastrointestinal tract will be examined and quantified using antibodies with specificity for individual gastrointestinal hormones, which antibodies have been labeled with specific fluorochromes. The capacity of gastrin to bind to parietal cells and/or to histamine-containing cells in human gastric mucosa will be examined. Gastrin peptides contained in, synthetized by, and released by antral and duodenal mucosal tissue will be characterized utilizing chromatographic and electrophoretic techniques, as well as immunochemical methods utilizing antibodies with precise specificity for limited regions of the gastrin molecule including those contained in and excluding the active site region.